Last Updated on June 30, 2023 by Steven Root


Crohn’s disease is a chronic, inflammatory bowel disorder. In this article, we provide a review of the Crohn’s disease autoimmune mechanisms, delving into:

  • The basics of Crohn’s disease
  • The autoimmune connection
  • How the immune system is implicated
  • The potential triggers
  • Treatment strategies based on autoimmune understanding

What is Crohn’s Disease?

Crohn’s disease is a type of inflammatory bowel disease (IBD) that can cause inflammation anywhere along the digestive tract. Symptoms include abdominal pain, diarrhea, weight loss, and fatigue and other systemic issues. It is named after Dr. Burrill B. Crohn, who first described the disease in 1932 (link).

The Autoimmune Component in Crohn’s Disease

Crohn’s disease has long been classified as an autoimmune disorder due to the involvement of the immune system in its pathology.

Understanding Autoimmunity

In an autoimmune response, the immune system mistakenly targets and attacks the body’s own cells and tissues. Normally, the immune system is designed to protect against foreign pathogens. However, in autoimmune conditions, it fails to distinguish between foreign substances and its own cells.

Chronic Inflammation

In Crohn’s disease, the autoimmune response leads to chronic inflammation, particularly in the digestive tract. This inflammation can cause the walls of the intestines to thicken and form ulcers, leading to many of the symptoms associated with Crohn’s disease.

Dysregulated Immune Response

The immune response in Crohn’s disease is dysregulated. This means that the normal checks and balances that keep the immune system in line are not functioning properly. This dysregulation can cause the immune system and it’s associated inflammation to remain active for longer than necessary, leading to tissue damage over time.

Potential Triggers

There are numerous factors that can trigger the autoimmune response in Crohn’s disease. These include genetic predisposition, environmental factors, and the presence of certain microbes in the digestive tract. Understanding these triggers can help in managing and treating the disease.

The Role of Immune Cells

In Crohn’s disease, certain immune cells, such as T cells, play a significant role in driving the autoimmune response. These cells release inflammatory substances that can damage the lining of the intestines.

The Errant Immune Response

Immune Reaction to Gut Bacteria

In Crohn’s disease, the immune system can abnormally react to certain gut bacteria, which are usually harmless. The immune response is hyperactive and fails to shut down, leading to continuous inflammation in the tissues of the gut (source).

Microbiome Imbalance

Later discussed, alterations in the balance of gut bacteria, known as the microbiome, are believed to play a role in the aberrant immune response. A healthy gut has a wide diversity of bacteria, but in Crohn’s disease, there is often less bacterial diversity. This associated imbalance can affect the immune response.

Intestinal Barrier Dysfunction

The lining of the intestine forms a barrier that prevents harmful substances from entering the bloodstream. In Crohn’s disease, this barrier becomes dysfunctional, often called Leaky Gut or intestinal permeability, allowing pathogens and foreign proteins to enter the various tissues of the body, triggering an autoimmune response.

Role of Immune Mediators

Cytokines are chemical messengers that play a key role in regulating the immune response. In Crohn’s disease, there is often an overproduction of pro-inflammatory cytokines, which can drive inflammation and contribute to tissue damage.

Finding the Off Switch

Understanding how to modulate the errant immune response in Crohn’s disease is a key research area. By learning how to turn off or down-regulate the over-active immune response, it may be possible to develop more effective treatments for this condition.

Genetic Predisposition

The Genetics of Crohn’s Disease

Genetic factors play a significant role in the susceptibility to Crohn’s disease. Studies have identified multiple gene mutations that are more common in people with Crohn’s disease (source).

NOD2 Gene

One of the most well-studied genes associated with Crohn’s disease is NOD2. This gene is involved in recognizing bacteria and regulating the immune response to bacteria in the gut. Mutations in NOD2 have been linked to an increased risk of developing Crohn’s disease.

Other Genetic Factors

Besides NOD2, there are many other genes associated with Crohn’s disease. These genes are involved in various functions such as immune response regulation, maintenance of the intestinal barrier, and microbial defense. See full article on Crohn’s disease genetics here.

Family History

Having a family member with Crohn’s disease significantly increases the risk of developing the condition. This is likely due to shared genetic factors that predispose family members to Crohn’s disease, although the transference of gut bacteria from mother to child is also an area of research.

Future Genetic Research

Understanding the genetic basis of Crohn’s disease can potentially lead to new treatments. By targeting the genetic abnormalities that contribute to the disease, it may be possible to develop therapies that can modify the course of the disease.

Environmental Factors

Role of Environment

Environmental factors play a critical role in triggering Crohn’s disease in individuals who are genetically predisposed. These factors can influence the composition of gut bacteria and the integrity of the intestinal wall, possibly triggering or exacerbating the autoimmune reaction (source).


Smoking has been shown to increase the risk of Crohn’s disease and is associated with a more severe course of the disease. The chemicals in cigarette smoke can affect the immune system and the lining of the intestines.

Antibiotic Use

The use of antibiotics, especially at a young age, has been linked to the development of Crohn’s disease. Antibiotics can alter the gut microbiome thereby altering the immune response to bacteria in the gut, which may play a role in the onset of the disease.

Sanitation and Hygiene

The “hygiene hypothesis” suggests that living in very clean environments during childhood can increase the risk of autoimmune diseases by not exposing the immune system to enough microbes, and leaving it ‘untrained’. An immune system that has been exposed to an array of microbes earlier in life seems not to over react to various pathogens and harmless microbes later in life.

Stress and Mental Health

Psychological stress and poor mental health have been implicated in the exacerbation of Crohn’s disease. Stress can affect the immune system, up-regulating the release of pro-inflammatory cytokines, leading to tissue damage in the gut.

Microbial Factors

The Gut Microbiome

The human gut contains trillions of microbes, including bacteria, viruses, and fungi. This community of microbes is known as the gut microbiome. It plays a vital role in digestion, immune function, and overall health. Disruptions in the microbiome are thought to be involved in the development of Crohn’s disease (source).

Specific Microbial Triggers

Research suggests that certain bacteria, such as Mycobacterium avium subspecies paratuberculosis, and viruses may play a role in triggering Crohn’s disease. These microbes are thought to interact with the immune system in such a way that initiates an autoimmune response.

Bacterial Overgrowth

An overgrowth of harmful bacteria in the gut, often at the expense of beneficial bacteria, may contribute to the development of Crohn’s disease. This imbalance is thought to lead to an inappropriate immune response.

Role of Fungi and Viruses

Besides bacteria, other microbes such as fungi and viruses are also being investigated for their role in Crohn’s disease. Like bacteria, they are thought to trigger the immune system and increase inflammation in the gut.

Probiotics and Microbial Balance

There is growing interest in the use of probiotics to restore a healthy balance of gut bacteria in people with Crohn’s disease, thereby helping to regulate the immune response. Probiotics are live bacteria that can confer health benefits when consumed in adequate amounts.

Lifestyle and Dietary Factors

Diet and Crohn’s Disease

Dietary changes can have a significant impact on the management of Crohn’s disease. A balanced diet can help reduce inflammation, support a healthy gut microbiome, and improve symptoms (source).

Diets high in processed foods and sugars and low in whole foods alter the microbiome, damage the gut lining, thereby affecting the immune response and increasing the likelihood of the onset of Crohn’s disease (source).

Enquire here for help in building a dietary strategy to mitigate against Crohn’s disease symptoms.

Processed Foods

Processed foods often contain additives and preservatives that can damage the gut lining, the microbiome, and therefore alter the immune response. This can potentially contribute to the development of Crohn’s disease.

Food Sensitivities

Some individuals with Crohn’s disease have sensitivities to certain foods, such as gluten or dairy. These sensitivities involve an over-activation of the immune system likely due to a dysfunctional gut lining and/or imbalanced microbiome.

Elimination Diets

Some individuals with Crohn’s disease find relief by following various elimination diets, where certain foods that may be triggering the immune system are removed from the diet to see if symptoms improve. Support in choosing an elimination diet suitable for you can be found here.

Stress Reduction

Stress management techniques such as meditation, yoga, mindfulness, and counseling can be beneficial in managing Crohn’s disease. Effective stress management can down-regulate the immune system’s production of pro-inflammatory cytokines, thereby reducing the frequency of Crohn’s disease symptoms and their severity.

Regular Exercise

Engaging in regular, moderate exercise can have benefits for people with Crohn’s disease. Exercise can reduce stress, support a healthy gut, and strengthen the immune system (source).


Immune System Altering Drugs

Medications that suppress the immune system, such as biologics, immunomodulators, and steroids are often used to treat Crohn’s disease. By reducing the activity of the immune system, these drugs can decrease inflammation in the gut (source).

Unfortunately these drugs can cause many side affects and it is important to discuss these side affects with your provider.


Antibiotics may be used to treat infections and complications of Crohn’s disease. However, they should be used cautiously as they can negatively affect the gut microbiome and gut lining, and even be causal of Crohn’s disease if they are misused.


  • Crohn’s disease is a chronic inflammatory bowel disease.
  • It involves an autoimmune response where the immune system attacks the digestive tract.
  • Genetic predisposition plays a significant role in the disease.
  • Environmental factors like diet and smoking can trigger or worsen the autoimmune reaction.
  • Microbial factors, particularly imbalances in gut bacteria, contribute to the disease’s development.
  • Medications like immunosuppressants and biologics are often used for treatment.
  • Lifestyle changes, including diet modifications, can help manage symptoms.

Understanding Crohn’s disease autoimmune mechanisms can help in developing better management and treatment strategies. Through diet and lifestyle changes, medication, and continued research, it’s possible to improve the quality of life for those affected by Crohn’s disease.